Alopecia manifests itself in various types including male pattern alopecia, alopecia senilis, alopecia areata, and alopecia in postmenopausal women. While alopecia is not life-threatening in many cases, the disease is cosmetically distressing and often involves mental pain; under the circumstances, effective agents for preventing or treating alopecia are desired.
Hairs are born again through three stages, the anagen, catagen, and telogen phases (hair cycle). One hair cycle usually takes a period of two to seven years to complete and if something abnormal occurs to shorten this period, hair growth is arrested before reaching maturity. As a consequence, more hairs will fall out to result in a lower hair density or the thickness per hair will decrease. Factors that upset the rhythm of hair cycle include androgens such as testosterone and dihydrotestosterone, radiation, medicaments such as anticancer drugs, aging, and stress.
Studies using many diverse compounds are being made with a view to creating therapeutics for alopecia, and the immunosuppressant FK506 (tacrolimus), for example, has been reported to have a recognizable hair-development stimulating effect in a plurality of animal models (see Patent Document 1 and Non-Patent Document 1.) The action of FK506 has been confirmed in models of alopecia areata which is considered an autoimmune disease (see Non-Patent Documents 2 and 3), as well as in hair development tests using normal mice and models of alopecia medicamentosa (see Non-Patent Documents 4 and 5.) However, due to its immunosuppressing action, FK506 has high risk for side-effects, so there is desired a safer compound that is effective as a therapeutic for alopecia without presenting the immunosuppressing action.
A plurality of compounds that bind to immunophilin FKBP12 (an FK506 binding protein with a molecular weight of 12 kDa) without exerting the immunosuppressing action have recently been found (see Patent Documents 2-10.) Some of those derivatives have been disclosed to show a hair-development stimulating action (see Patent Documents 11 and 12.) Other derivatives, however, have not been reported to show any hair-development stimulating action and much remains unclear about the relationship between the activity of binding to immunophilin FKBP12 and the hair-development stimulating activity. What is more, the reported FKBP12 binding compounds are not disclosed to have the same azole structures as specified in the present invention.